![]() ![]() This general chapter is harmonized with the corresponding texts of the European Pharmacopoeia and/or the Japanese Pharmacopoeia. These pharmacopeias have undertaken not to make any unilateral change to this harmonized chapter.
Portions of the present general chapter text that are national USP text, and therefore not part of the harmonized text, are marked with symbols (
![]() ![]() This test is provided to determine compliance with the dissolution requirements
![]() ![]() ![]() USP Reference Standards ![]() ![]() ![]() APPARATUS
Apparatus 1 (Basket Apparatus)
The assembly consists of the following: a vessel, which may be covered, made of glass or other inert, transparent material1; a motor; a metallic drive shaft; and a cylindrical basket. The vessel is partially immersed in a suitable water bath of any convenient size or heated by a suitable device such as a heating jacket. The water bath or heating device permits holding the temperature inside the vessel at 37 ± 0.5
![]() ![]() ![]() ![]() ![]() ![]() ![]() Shaft and basket components of the stirring element are fabricated of stainless steel, type 316, or other inert material, to the specifications shown in Figure 1. A basket having a gold coating of about 0.0001 inch (2.5 µm) thick may be used. A dosage unit is placed in a dry basket at the beginning of each test. The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 ± 2 mm during the test.
Apparatus 2 (Paddle Apparatus)
Use the assembly from Apparatus 1, except that a paddle formed from a blade and a shaft is used as the stirring element. The shaft is positioned so that its axis is not more than 2 mm from the vertical axis of the vessel at any point and rotates smoothly without significant wobble that could affect the results. The vertical center line of the blade passes through the axis of the shaft so that the bottom of the blade is flush with the bottom of the shaft. The paddle conforms to the specifications shown in Figure 2. The distance of 25 ± 2 mm between the bottom of the blade and the inside bottom of the vessel is maintained during the test. The metallic or suitably inert, rigid blade and shaft comprise a single entity. A suitable two-part detachable design may be used provided the assembly remains firmly engaged during the test. The paddle blade and shaft may be coated with a suitable coating so as to make them inert. The dosage unit is allowed to sink to the bottom of the vessel before rotation of the blade is started. A small, loose piece of nonreactive material, such as not more than a few turns of wire helix, may be attached to dosage units that would otherwise float. An alternative sinker device is shown in Figure 2a. Other validated sinker devices may be used.
Apparatus 3 (Reciprocating Cylinder)
not accepted by the japanese pharmacopoeia
The assembly consists of a set of cylindrical, flat-bottomed glass vessels; a set of glass reciprocating cylinders; inert fittings (stainless steel type 316 or other suitable material), and screens that are made of suitable nonsorbing and nonreactive material and that are designed to fit the tops and bottoms of the reciprocating cylinders; and a motor and drive assembly to reciprocate the cylinders vertically inside the vessels and, if desired, index the reciprocating cylinders horizontally to a different row of vessels. The vessels are partially immersed in a suitable water bath of any convenient size that permits holding the temperature at 37 ± 0.5
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Apparatus 4 (Flow-Through Cell)
The assembly consists of a reservoir and a pump for the Dissolution Medium; a flow-through cell; and a water bath that maintains the Dissolution Medium at 37 ± 0.5
![]() ![]() ![]() The pump forces the Dissolution Medium upwards through the flow-through cell. The pump has a delivery range between 240 and 960 mL per hour, with standard flow rates of 4, 8, and 16 mL per minute. It must deliver a constant flow (±5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 ± 10 pulses per minute. A pump without pulsation may also be used. Dissolution test procedures using a flow-through cell must be characterized with respect to rate and any pulsation.
The flow-through cell (see Figures 4 and 5), of transparent and inert material, is mounted vertically with a filter system (specified in the individual monograph) that prevents escape of undissolved particles from the top of the cell; standard cell diameters are 12 and 22.6 mm; the bottom cone is usually filled with small glass beads of about 1-mm diameter with one bead of about 5 mm positioned at the apex to protect the fluid entry tube; and a tablet holder (see Figures 4 and 5) is available for positioning of special dosage forms, for example, inlay tablets. The cell is immersed in a water bath, and the temperature is maintained at 37 ± 0.5
![]() Figure 4. Apparatus 4, large cell for tablets and capsules (top), tablet holder for the large cell (bottom). (All measurements are expressed in mm unless noted otherwise.)
Figure 5. Apparatus 4, small cell for tablets and capsules (top), tablet holder for the small cell (bottom). (All measurements are expressed in mm unless noted otherwise.)
The apparatus uses a clamp mechanism and two O-rings to assemble the cell. The pump is separated from the dissolution unit in order to shield the latter against any vibrations originating from the pump. The position of the pump should not be on a level higher than the reservoir flasks. Tube connections are as short as possible. Use suitably inert tubing, such as polytef, with about 1.6-mm inner diameter and chemically inert flanged-end connections.
apparatus suitability
The determination of suitability of a test assembly to perform dissolution testing must include conformance to the dimensions and tolerances of the apparatus as given above. In addition, critical test parameters that have to be monitored periodically during use include volume and temperature of the Dissolution Medium, rotation speed (Apparatus 1 and Apparatus 2), dip rate (Apparatus 3), and flow rate of medium (Apparatus 4).
Determine the acceptable performance of the dissolution test assembly periodically.
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Performance Verification Test, Apparatus 1 and 2
Test USP Prednisone Tablets RS according to the operating conditions specified. The apparatus is suitable if the results obtained are within the acceptable range stated in the technical data sheet specific to the lot used and the apparatus tested.
Performance Verification Test, Apparatus 3
[To come.]
Performance Verification Test, Apparatus 4
[To come.]
![]() PROCEDURE
Apparatus 1 and Apparatus 2
immediate-release dosage forms
Place the stated volume of the Dissolution Medium (±1%) in the vessel of the specified apparatus
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() If automated equipment is used for sampling or the apparatus is otherwise modified, verification that the modified apparatus will produce results equivalent to those obtained with the standard apparatus described in this general chapter is necessary.
Dissolution Medium
A suitable dissolution medium is used. Use the solvent specified
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Time
Where a single time specification is given, the test may be concluded in a shorter period if the requirement for minimum amount dissolved is met. Specimens are to be withdrawn only at the stated times within a tolerance of ±2%.
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extended-release dosage forms
Proceed as directed for Immediate-Release Dosage Forms.
Dissolution Medium
Proceed as directed for Immediate-Release Dosage Forms.
Time
The test-time points, generally three, are expressed in hours.
delayed-release dosage forms not accepted by the japanese pharmacopoeia
Use Method A or Method B and the apparatus specified
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Method A
Procedure
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acid stage
Place 750 mL of 0.1 N hydrochloric acid in the vessel, and assemble the apparatus. Allow the medium to equilibrate to a temperature of 37 ± 0.5
![]() ![]() ![]() After 2 hours of operation in 0.1 N hydrochloric acid, withdraw an aliquot of the fluid, and proceed immediately as directed under Buffer Stage.
Perform an analysis of the aliquot using a suitable assay method.
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buffer stage
[NoteComplete the operations of adding the buffer and adjusting the pH within 5 minutes. ]
With the apparatus operating at the rate specified
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Method B
Procedure
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acid stage
Place 1000 mL of 0.1 N hydrochloric acid in the vessel, and assemble the apparatus. Allow the medium to equilibrate to a temperature of 37 ± 0.5
![]() ![]() ![]() Perform an analysis of the aliquot using a suitable assay method.
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buffer stage
[NoteFor this stage of the procedure, use buffer that previously has been equilibrated to a temperature of 37 ± 0.5
![]() Continue to operate the apparatus for 45 minutes, or for the specified time
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Apparatus 3 (Reciprocating Cylinder)
not accepted by the japanese pharmacopoeia immediate-release dosage forms
Place the stated volume of the Dissolution Medium in each vessel of the apparatus, assemble the apparatus, equilibrate the Dissolution Medium to 37 ± 0.5
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Dissolution Medium
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 1 and Apparatus 2.
Time
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 1 and Apparatus 2.
extended-release dosage forms
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 3.
Dissolution Medium
Proceed as directed for Extended-Release Dosage Forms under Apparatus 1 and Apparatus 2.
Time
Proceed as directed for Extended-Release Dosage Forms under Apparatus 1 and Apparatus 2.
delayed-release dosage forms
Proceed as directed for Delayed-Release Dosage Forms, Method B under Apparatus 1 and Apparatus 2 using one row of vessels for the acid stage media and the following row of vessels for the buffer stage media and using the volume of medium specified (usually 300 mL).
Time
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 1 and Apparatus 2.
Apparatus 4 (Flow-Through Cell)
immediate-release dosage forms
Place the glass beads into the cell specified
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Dissolution Medium
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 1 and Apparatus 2.
Time
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 1 and Apparatus 2.
extended-release dosage forms
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 4.
Dissolution Medium
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 4.
Time
Proceed as directed for Immediate-Release Dosage Forms under Apparatus 4.
delayed-release dosage forms
Proceed as directed for Delayed-Release Dosage Forms under Apparatus 1 and Apparatus 2, using the specified media.
Time
Proceed as directed for Delayed-Release Dosage Forms under Apparatus 1 and Apparatus 2.
INTERPRETATION
Immediate-Release Dosage Forms
Unless otherwise specified
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Acceptance Table 1
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Acceptance Table for a Pooled Sample
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Extended-Release Dosage Forms
Unless otherwise specified
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Acceptance Table 2
Delayed-Release Dosage Forms
not accepted by the japanese pharmacopoeia
Acid Stage
Unless otherwise specified
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Acceptance Table 3
Buffer Stage
Unless otherwise specified
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Acceptance Table 4
1
The materials should not sorb, react, or interfere with the specimen being tested.
2
If a cover is used, it provides sufficient openings to allow ready insertion of the thermometer and withdrawal of specimens.
3
Test specimens are filtered immediately upon sampling unless filtration is demonstrated to be unnecessary. Use an inert filter that does not cause adsorption of the active ingredient or contain extractable substances that would interfere with the analysis.
4
One method of deaeration is as follows: Heat the medium, while stirring gently, to about 41
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Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP38NF33 Page 486
Pharmacopeial Forum: Volume No. 40(6)
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